The impact of intravenous heroin use on immune activation in treated HIV

这项申请的提案将研究免疫激活的程度和细节，其心血管功能， 结果和机制，因为它们与HIV感染的静脉注射（IV）海洛因使用者的肠道完整性有关 在抗逆转录病毒治疗中病毒学受到抑制。超越目标是1）定义范围和细节 HIV感染的IV海洛因使用者的免疫激活; 2）确定IV海洛因对肠道完整性的影响， 渗透性，以及肠道完整性改变与免疫激活的关系; 3）重要的是，研究 停止静脉注射海洛因后免疫激活、炎症和肠道功能障碍的可逆性， 两种药物辅助治疗策略效果比较-丁丙诺啡/纳洛酮与美沙酮 维持; 4）研究是否与主动静脉注射药物（IVDU）相关的免疫激活增强 与较高的心血管疾病风险相关，包括内皮功能障碍和动脉粥样硬化。 炎症，以及这些作用是否可以用丁丙诺啡/纳洛酮或美沙酮逆转。回答这些 一个专家小组已经组建了一个计划，招募一批接受过抗逆转录病毒治疗的艾滋病毒感染者， 使用静脉注射海洛因的感染者，以及从未使用过静脉注射海洛因的HIV感染者对照组 毒品第二组接受抗逆转录病毒疗法治疗的艾滋病毒感染者使用静脉注射海洛因， 还将建立使用丁丙诺啡/纳洛酮或美沙酮停止使用的治疗。这些 将对队列进行连续随访，并收集关于病毒学和免疫学应答的数据， 继续静脉注射海洛因与不使用静脉注射毒品，丁丙诺啡/纳洛酮与美沙酮。水平的细胞 活化与T淋巴细胞的表型，以及免疫活化的可溶性标志物的水平， 将测量炎症。静脉留置针对动脉炎症和内皮细胞的影响及其可逆性 在丁丙诺啡/纳洛酮或美沙酮之前和之后连续测量功能障碍。

The proposal in this application will study the extent and specifics of immune activation, its cardiovascular consequences, and mechanisms as they relate to gut integrity in HIV-infected intravenous (IV) heroin users virologically-suppressed on antiretroviral therapy. Overreaching goals are 1) to define the extent and specifics of immune activation in HV-infected IV heroin users; 2) to define the effect of IV heroin on gut integrity and permeability, and the relationship of gut integrity alteration and immune activation; 3) importantly, to study the reversibility of immune activation, inflammation, and gut dysfunction after cessation of IV heroin, and to that effect, compare two strategies for medication assisted treatment—buprenorphine/naloxone versus methadone maintenance; 4) to study if heightened immune activation associated with active intravenous drug use (IVDU) is associated with higher cardiovascular disease risk, including endothelial dysfunction and arterial inflammation, and if these effects are reversible with buprenorphine/naloxone or methadone. To answer these complex questions an expert team has been assembled with the plan to recruit a cohort of ART-treated, HIV- infected persons who use IV heroin, and very carefully matched HIV-infected controls who have never used IV drugs. A second cohort of ART-treated HIV-infected persons who use IV heroin choosing medication assisted treatment with either buprenorphine/naloxone or methadone to stop using will also be established. These cohorts will be followed serially and data will be collected regarding virologic and immunologic responses to continued IV heroin use versus no IVDU and to buprenorphine/naloxone versus methadone. Levels of cellular activation with phenotyping of T-lymphocytes, as well as levels of soluble markers of immune activation and inflammation will be measured. The effect and reversibility of IVDU on arterial inflammation and endothelial dysfunction will be serially measured, before and after buprenorphine/naloxone or methadone.